Human endometrial epithelium exhibits regional specific changes throughout the menstrual cycle. This includes differential expression of HLA-DR and proliferation in the proliferative phase and apoptosis and cell-cell dissociation in the secretory/menstrual phases. Based on the premise that lymphoid aggregates in the basalis contain activated T cells, we proposed the differential interferon (IFN)-gamma secretion as a basis for preferential HLA-DR expression & inhibition of proliferation of endometrial epithelium in the basalis during the proliferative phase. Evidence-for activation of endometrial T cells preferentially localized in the basalis, secretion of IFN-gamma by these cells,induction of HLA-DR expression and inhibition of proliferation of endometrial epithelium by this cytokine all supported this concept. Furthermore, we have identified a new pathway by which the epithelial cell properties may be modulated by T cells. This novel cell-cell communication pathway consists of interaction of cells with vesicles shed from T cells that encompass T cell associated proteins including TNF-alpha. Based on these findings, we propose that the effect of T cells and their products continues in the secretory/menstrual phases and may be implicated in the apoptosis and dysochesion of endometrial epithelium during the secretory/menstrual phases. Therefore, the goals of this proposal is to examine the role of T cells in these specific attributes of epithelial cells and to study whether such epithelial cell properties are differentially regulated by the T cell signals. Clearly, these studies are essential in identifying the active role of T cells in the machinery that drives human endometrium throughout menstrual cycles and prime it for conception. Such information will also serve as a basis for understanding the T cell signals that potentially impair endometrial function resulting in such common manifestations as bleeding, abnormal menstruation and infertility.